Effect of arsenite exposure on the expression of fibrinolytic system factors in mouse vascular tissues

<p>Chronic arsenic exposure is known to cause vascular diseases such as atherosclerosis, but the toxic mechanisms remain largely unknown. We have previously reported that arsenite affects the expression of factors involved in the coagulation and fibrinolytic systems in cultured vascular component cells. In this study, we examined the expression of fibrinolytic factors, tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), and their inhibitor, plasminogen activator-1 (PAI-1).</p><p>Male C57BL6/J mice aged 7 weeks were intraperitoneally administered (3, 24 hours, and 2 weeks) with saline (10 mL/kg/day) or sodium arsenite (1.5, 3, 5 mg/kg/day as total dose of arsenic), and then thoracic aorta, perivascular adipose tissue (PVAT) and serum were collected. The expression levels of mRNA were determined by real-time RT-PCR, and serum t-PA levels were measured by ELISA kit.</p><p>At 3 hours after arsenite administration, t-PA and u-PA mRNA levels were significantly decreased in PVAT, but no such changes were observed in thoracic aorta. In thoracic aorta treated with arsenite for 2 weeks, t-PA and u-PA mRNA levels were significantly decreased, but PAI-1 mRNA levels were unchanged. On the other hand, no significant changes were observed in PVAT. Significant reductions in serum t-PA levels were also observed after 24 hours and 2 weeks of arsenite administration. These results indicate that arsenite exposure induces a decrease in the expression of fibrinolytic factors t-PA and u-PA in the thoracic aorta and PVAT, as well as a decrease in the amount of t-PA in mouse serum.</p>